Blood pressure, hematologic and biochemical changes following L-arginine supplementation in children with sickle cell anaemia already on hydroxyurea therapy.

Hydroxyurea is an approved therapy in the management of children suffering from sickle cell disease (SCD). In adults co-administration of hydroxyurea and L-Arginine in adult sufferers of SCD had shown some benefits. This study examined the effect of co-administration of hydroxyurea (15-35mg/kg/day) and L-Arginine (500 mg/day) for 6 weeks on blood pressure, haematological parameters, liver and antioxidant enzymes levels. The levels of these parameters when the subjects were on hydroxyurea alone were taken as control values. Results showed that the combined therapy (HU + L-Arginine) decreased SBP, DBP, MAP and PP (p <0.01 in each case) but increased %HbF, Hb and PCV (p< o.001 in each case). It elevated CAT, SOD, GPX (p < 0.001 in each case) but depressed MDA, AST, ALT and ALP (p < 0.001 in each case). The study shows that L-Arginine used as an adjunct to hydroxyurea therapy may be beneficial to children suffering from sickle cell anaemia.

l-Arginine supplementation enhances antioxidant activity and erythrocyte integrity in sickle cell anaemia subjects.

The effect of oral, low-dose l-arginine supplementation (1g/day for 6 weeks) on antioxidant activity, haematological parameters and osmotic fragility of red blood cells was investigated in sickle cell disease sufferers. Twenty eight sickle cell anaemia subjects were recruited for the study. Five millilitres of blood was withdrawn from an ante-cubital vein for the estimation of plasma arginine concentration ([R]), total antioxidant enzymes (TAE) activity, malondialdehyde concentration ([MDA]), RBC count, [Hb], PCV, MCHC, MCV, MCH, percent irreversibly sickled cells (%ISC)) and osmotic fragility of red blood cells in the subjects. l-arginine supplementation increased [R] (p<0.001), TAE activity (p<0.05) and MCV (<0.05) but reduced plasma [MDA], MCHC, MCH and %ISC (p<0.001, respectively). Δ[R] correlated positively with ΔTAE (r=0.8) and negatively with Δ[MDA] (r=-0.7) and Δ%ISC (r=-0.5). Also ΔTAE activity correlated negatively with Δ[MDA] (r=-0.7) and Δ%ISC (r=-0.6). Supplementation shifted the osmotic fragiligram to the right and reduced the concentrations of NaCl at which initial and complete lyses of erythrocytes occurred. Study showed that low-dose, oral l-arginine increased antioxidant activity, red blood cell resistance to osmotic lysis but reduced red cell density in SCD.

L-arginine increases nitric oxide and attenuates pressor and heart rate responses to change in posture in sickle cell anemia subjects.

Pressor and heart rate changes following change in posture without or with L-arginine supplementation (1g/day for 6 weeks) were studied in 28 sickle cell anemia (SCA) and 32 non-sickle cell anemia (NSCA) subjects. Change in posture increased HR (p<0.01), RPP (p<0.05) in both groups of subjects, MABP (p<0.05) in SCAS but reduced MABP (p<0.01) in NSCAS and PP (p<0.01) in SCAS. L-Arginine supplementation increased plasma L-Arginine concentration ([R]) in both groups of subjects (p<0.001 in each group) and serum nitric oxide metabolites concentration ([NOx]) (p<0.01 in each group). Change (Δ) [R] correlated positively with Δ [NOx] in both groups (+ 0.7 in each group). L-Arginine supplementation caused greater reduction of MABP (p<0.001) in NSCAS than in SCAS. However, reduction in HR was greater (p<0.001) in SCAS than in NSCAS. After supplementation, MABP and PP responses to change in posture were attenuated in the two groups. However, while HR and RPP responses in SCAS were attenuated, the same responses were enhanced in NSCAS by change in posture after supplementation. In conclusion, study shows that oral, low dose, chronic supplementation with L-arginine increased NO availability and attenuated pressor and heart rate responses to change in posture in sickle cell anemia subjects.

Electrocardiographic and blood pressure changes in apparently healthy male subjects following oral, chronic, low-dose vitamin C supplementation and/or change in posture.

INTRODUCTION: Studies have shown that oral, chronic, low dose vitamin C reduces blood pressure and forearm blood flow in normal young adults or hypertensive patients. It is not clear how vitamin C affects cardiac function or autonomic control of blood pressure in young apparently healthy adults. AIM: This study was undertaken to examine the effects of a chronic, low dose (300 mg/day for 6 weeks) vitamin C supplementation on the electrocardiogram and autonomic control of blood pressure in apparently healthy male subjects. METHODOLOGY: Electrocardiographic (ECG) and arterial blood pressure (BP) changes were assessed following change in posture with or without oral, chronic low dose vitamin C supplementation in twenty (20) apparently healthy male subjects (mean age 28.2 +/- 2.0 yrs). Blood pressure (BP, mm Hg) and ECG measurements (amplitude, mV; duration or interval, ms) were recorded in the supine position and immediately on assumption of the upright position. Heart rate (HR; beats/min) was calculated from the ECG while rate pressure product (RPP; arbitrary units) was calculated and used as a measure of myocardial oxygen demand. Each subject was then placed on oral vitamin C at a dose of 300 mg/day for 6 weeks. Measurements were made again after the period. RESULTS: Change in posture caused significant reductions in P-wave amplitude, QRS amplitude and duration, T-wave amplitude and systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial blood pressure (MABP) (p < 0.01 respectively). PR and RR intervals also fell (p < 0.05 and p < 0.001 respectively) while HR and RPP increased (p < 0.001) Vitamin C decreased T-wave amplitude (p < 0.01) and QRS duration (p < 0.01). Also, SBP, DBP, MABP and RPP fell (p < 0.01 in each case). After vitamin C supplement ation, change in posture decreased P-wave amplitude, T-wave duration, P-wave duration, QT interval and RR interval (p < 0.05 respectively). BP and HR responses to postural change were attenuated by vitamin C supplementation. SBP fell by 7.4 +/- 1.0 mm Hg (Vs 12.2 +/-0.1 mm Hg pre-supplementation), DBP by 5.4 +/- 0.6 mm Hg (Vs 10.4 +/- 0.1 mm Hg pre-supplementation) and MABP by 6.1 +/- 1.4 mm Hg (Vs 11.0 +/- 0.1 mm Hg pre-supplementation). HR increased by 18.6 +/- 1.0 beats/min (Vs 29.6 +/- 2.5 beats/min pre-supplementation) and RPP by 1385.6 +/- 126.4 units (Vs 2370.0 +/- 105.6 units pre-supplementation). CONCLUSION: Chronic, low dose vitamin C supplementation enhanced cardiovascular autonomic activity in apparently healthy young subjects. It minimized the fluctuations in BP and HR and also reduced myocardial oxygen demand following postural change.

Cardiac and autonomic responses to change in posture or vitamin C supplementation in sickle cell anemia subjects.

Autonomic function following change in posture with or without vitamin C supplementation was studied in ten (10) sickle cell anemia (SCA) and twelve (12) non-sickle cell anemia (NSCA) subjects. Arterial blood pressure and electrocardiographic measurements were taken in the supine position on a couch 80cm high and immediately on assumption of the upright position. Vitamin C was then administered orally (300mg/day for 6 weeks). At the end of the period, blood pressure and ECG measurements were again made in the supine position and in response to change in posture. Change in posture significantly decreased QRS amplitude, QRS duration, PR interval, RR interval and MABP but increased HR and rate pressure product (RPP) in both groups of subjects. The HR and RPP responses were significantly higher in NSCA than in SCA subjects (p<0.001, respectively). Vitamin C caused greater reductions in QRS duration (p<0.01), PR duration p<0.001) in the NSCA subjects than in SCA subjects. It caused, however, greater reduction in RR duration (p<0.001) and MABP in SCA subjects than in NSCA subjects. It also caused significantly greater increases in HR and RPP (p<0.001, respectively) in the SCA subjects than in NSCA subjects. After vitamin C supplementation, change in posture decreased RR interval (p<0.001), QT interval (p<0.01) and MABP (p<0.05) but increased RPP (p<0.01) in NSCA subjects. In SCA subjects, there was a fall in RR interval (p<0.001) and MABP (p<0.01), but elevated RPP (p<0.001). Changes (Delta) in MABP, HR and RPP were similar between NSCA and SCA subjects. In conclusion, these findings indicate a blunted cardiovascular autonomic response to change in posture in sickle cell anemia subjects. Chronic, oral, low-dose vitamin C supplementation equilibrates this response with those of non-sickle cell anemia subjects.